Potential coordination role between O-GlcNAcylation and epigenetics

Abstract

Dynamic changes of the post-translational O-GlcNAc modification (O-GlcNAcylation) are controlled by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the glycoside hydrolase O-GlcNAcase (OGA) in cells. O-GlcNAcylation often occurs on serine (Ser) and threonine (Thr) residues of the specific substrate proteins via the addition of O-GlcNAc group by OGT. It has been known that O-GlcNAcylation is not only involved in many fundamental cellular processes, but also plays an important role in cancer development through various mechanisms. Recently, accumulating data reveal that O-GlcNAcylation at histones or non-histone proteins can lead to the start of the subsequent biological processes, suggesting that O-GlcNAcylation as 'protein code' or 'histone code' may provide recognition platforms or executive instructions for subsequent recruitment of proteins to carry out the specific functions. In this review, we summarize the interaction of O-GlcNAcylation and epigenetic changes, introduce recent research findings that link crosstalk between O-GlcNAcylation and epigenetic changes, and speculate on the potential coordination role of O-GlcNAcylation with epigenetic changes in intracellular biological processes.

Keywords: O-GlcNAcylation; epigenetics; histone modification; post-translational modification.

Figure 1

The process of O -GlcNAc modification and the molecular structure of OGT isoforms. A range of 2%–3% glucose uptake by the cells goes through the HBP pathway, experiences a series of modification and synthesize UDP-GlcNAc, the substrates of O-GlcNAc reaction. OGT/OGA are the enzymes in charge of add/remove UDP-GlcNAc at Ser or Thr residues respectively to control the balance of intracellular O-GlcNAcylation level. The molecular structure of 3 isoforms of OGT is highly conserved. By alternative splicing, 3 isoforms of OGT including nucleocytoplasmic isoform (ncOGT, 116 kDa), the mitochondrial isoform (mOGT, 103 kDa), and the short isoform (sOGT, 75 kDa) are produced.

Figure 2

Regulation and function of OGT-mediated protein complexes

Figure 3

Crosstalk between O -GlcNAcylation and chromatin remodelers. Extensive connections of O-GlcNAcylation with chromatin modifiers are detected in cells

Figure 4

Schematic diagram of coordination between OGT-mediated O -GlcNAcylation and chromatin remodelers in intracellular fundamental functions